Pets are often infested with one or more parasites that feed on blood, such as cat or dog fleas, ticks, or mange.
Fleas are wingless insects, with a laterally compressed body and highly developed legs, adapted for jumping. They are ectoparasites, which suck the blood of mammals or birds. The approximately 2000 listed species belong to the order of Siphonaptera. Two species of flea are commonly encountered in Europe; they are the cat flea (Ctenocephalides felis) and the dog flea (Ctenocephalides canis) which live in the animals' fur. The cat flea, which is the most common, is capable of reproducing both on cats and dogs. It can also attack man and other pets, but cats are the main host responsible for infestation when cats and dogs live in the same environment.
Fleas have a complex life cycle with four distinct stages: egg, larva, nymph and adult. They mate within the first 8 to 48 hours following acquisition by the host, after their first blood meal. The females thus begin to lay 24 to 48 hours after this first blood meal. The adult flea generally lays on the animal. The eggs laid on the animal do not remain thereon, but fall to the floor. Under optimum conditions, the female may lay more than 25 eggs per day. She will lay several hundred in her lifetime. After a few days, a white, hairy, worm-like larva about 1.5 mm long is born. The larva feeds on organic debris, larval remains and dry blood excreted by the adults. The larval state lasts for 1 to 3 weeks, if the conditions are favorable (18° to 27° C. and 70% relative humidity). The larva then spins a cocoon and transforms into a nymph. Normally, the nymph develops in 1 to 2 weeks, but passage to the adult state may take up to 1 year, if the conditions are unfavorable. The adult flea (small and black) emerges from the cocoon when it detects vibrations, heat and a higher concentration of carbon dioxide, which takes place during the passage of a cat, a dog . . . or a human! It then jumps onto the victim, feeds immediately on its blood and rapidly becomes engorged, taking a lighter reddish-brown color. The adult flea lives for 6 to 12 months. Without food, it can survive for up to 2 months.
Flea bites cause itching, in animals and in man. Flea saliva (secreted at each bite) may also, depending on the individual, lead to immediate or delayed allergic reactions. These reactions are reflected by various skin lesions and itching. Two types of flea-related dermatosis are distinguished, namely pulicosis and flea-bite allergic dermatitis. Whereas, in both cases, the dermatosis results from a more or less pronounced infestation with fleas, it is only in the second case that an allergic phenomenon is associated. Flea-bite allergic dermatitis (FBAD) is the most frequent cause of pruritus in dogs. In France, in adult dogs, it thus represents close to half the pruriginous dermatoses. Close to 80% of dogs presenting FBAD also have atopic dermatitis. Reciprocally, two out of three atopic dogs have FBAD. It is thus likely that atopic dogs are predisposed to developing a flea-bite allergy and that infestation with fleas is a triggering factor for atopic dermatitis. This justifies the need for very rigorous antiflea control in the case of atopic dogs or dogs belonging to at-risk breeds. Furthermore, FBAD is probably the main cause of reappearance of pruritus in the case of desensitized atopic dogs.
Fleas of the genus Ctenocephalides are moreover intermediate hosts of Dipylidium caninum, which is a parasitic worm of the small intestine of cats and dogs. The carnivore becomes infested by swallowing the parasitized fleas. This infestation may lead to anal pruritus, engorgement of the anal sacs, and also to dermatitis of the perineal region. This is why it is occasionally recommended to regularly worm animals in addition to combating fleas.
Similarly, ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp., Amblyomma sp., etc.) may also cause the animal stress and be harmful to its health. They may also be harmful to man. However, the most serious problem concerning ticks is that they are a vector of pathogens that affect animals as much as man. Among the major diseases that need to be avoided, mention may be made of Borellioses (Lyme's disease caused by Borellia burgdorferi), Babesioses (piroplasmoses caused by Babesia sp.) and Rickettsioses. Ticks may also release toxins with paralyzing and inflammatory, and occasionally fatal, properties.
Mange (Demodex sp., Sarcoptes sp., Otodectes sp., etc.) is particularly difficult to combat since there are very few efficient active materials. It requires frequent treatments.
Infestation with these various parasites, and most particularly with fleas, thus represents a major health problem for the infested animals and imposes the need for suitable treatments. The treatment should in particular not only have immediate efficacy (fast-acting) but also prolonged efficacy over time (remanence) so as to avoid, on the one hand, repeated treatments, and, on the other hand, any risk of infestation and/or reinfestation for a prolonged period. The flea, in particular, must be eliminated before it reproduces and begins to lay.
Many insecticidal substances that are more or less active and more or less expensive exist. Resistance phenomena appear associated with their use, and this is especially the case during the use of carbamates, organophosphorus compounds and pyrethroids.
Moreover, patent applications EP 0 295 117 and EP 0 352 944 describe a large family of N-phenyl-pyrazoles with a very broad spectrum of activity, including antiparasitic activity.
Although effective, N-phenylpyrazole derivatives, and in particular 5-amino-1-[2,6-dichloro-4-(trifluoro-methyl)phenyl]-4-(trifluoromethylsulfinyl)-1H-pyrazole-3-carbonitrile (fipronil), are occasionally difficult to formulate since they do not always have sufficient solubility in the excipients conventionally used for the preparation of ready-to-use liquid antiparasitic compositions.
Specifically, products that are active against blood-sucking parasites, and in particular against fleas, may especially be in the form of liquid compositions (pipettes) or solutions for applying to the skin, also known as “Spot-On solutions”, to be applied very easily, in a single topical application directly to the animal's skin, generally between the shoulder blades.
However, in this type of composition, fipronil is often difficult to formulate and may lead to crystallization. In order to overcome this problem, it has already been proposed, especially in patent application EP 0 881 881, to formulate N-phenylpyrazole derivatives in solvent medium in the presence of a crystallization inhibitor and a C1-C4 alcohol. The product Frontline® Spot-On Chat et Chien, sold in France by the company Merial SAS, is based on this technology.
Although such compositions are suitable for preventing the crystallization problems of these particular active principles, they are, however, not entirely satisfactory as regards the duration of protection they give the animal. In the case of the product Frontline® Spot-On Chat et Chien especially, the duration of protection against new flea infestations stated by the manufacturer is limited to 4 weeks in the case of cats and to 2 months in the case of dogs. However, antiparasitic efficacy tests conducted according to the current standards do not make it possible to reproduce the prolonged efficacy results, and the product does not therefore always have entirely satisfactory remanence.